The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods
Identifieur interne : 000160 ( Ncbi/Merge ); précédent : 000159; suivant : 000161The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods
Auteurs : Nasr Ya Hemdan [Allemagne, Égypte]Source :
- Journal of Occupational Medicine and Toxicology (London, England) [ 1745-6673 ] ; 2008.
Abstract
Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation.
Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed
Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios
It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.
Url:
DOI: 10.1186/1745-6673-3-25
PubMed: 18990205
PubMed Central: 2585571
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation.</p>
</sec>
<sec sec-type="methods"><title>Methods</title>
<p>Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed <italic>Salmonella enterica</italic>
, were cultured in the absence or presence of cadmium (Cd) acetate or mercuric (Hg) chloride. <italic>In vivo </italic>
experiments were set up where BALB/c mice were exposed to sub-lethal doses of Cd or Hg salts for 3 or 5 weeks. Cytotoxicity was assessed by MTT-reduction assay. Modulation of cytokine profiles was evaluated by enzyme-linked immunosorbent assay (ELISA), cytometric bead-based array (CBA) and real-time polymerase chain reaction (RT-PCR); the relevance of these methods of cytokine quantification was explored.</p>
</sec>
<sec><title>Results</title>
<p>Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios <italic>in vivo </italic>
correlated significantly with up- or down-regulation of IL-12 levels in both cases of investigated metals.</p>
</sec>
<sec><title>Conclusion</title>
<p>It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Occup Med Toxicol</journal-id>
<journal-title>Journal of Occupational Medicine and Toxicology (London, England)</journal-title>
<issn pub-type="epub">1745-6673</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
</publisher>
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<article-meta><article-id pub-id-type="pmid">18990205</article-id>
<article-id pub-id-type="pmc">2585571</article-id>
<article-id pub-id-type="publisher-id">1745-6673-3-25</article-id>
<article-id pub-id-type="doi">10.1186/1745-6673-3-25</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods</article-title>
</title-group>
<contrib-group><contrib id="A1" corresp="yes" contrib-type="author"><name><surname>Hemdan</surname>
<given-names>Nasr YA</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<xref ref-type="aff" rid="I2">2</xref>
<xref ref-type="aff" rid="I3">3</xref>
<email>nasr.hemdan@izi.fraunhofer.de</email>
</contrib>
</contrib-group>
<aff id="I1"><label>1</label>
Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany</aff>
<aff id="I2"><label>2</label>
Institute of Clinical Immunology and Transfusion Medicine – IKIT, Faculty of Medicine, University of Leipzig, Germany</aff>
<aff id="I3"><label>3</label>
Department of Zoology, Faculty of Science, University of Alexandria, Egypt</aff>
<pub-date pub-type="collection"><year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>6</day>
<month>11</month>
<year>2008</year>
</pub-date>
<volume>3</volume>
<fpage>25</fpage>
<lpage>25</lpage>
<ext-link ext-link-type="uri" xlink:href="http://www.occup-med.com/content/3/1/25"></ext-link>
<history><date date-type="received"><day>17</day>
<month>6</month>
<year>2008</year>
</date>
<date date-type="accepted"><day>6</day>
<month>11</month>
<year>2008</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2008 Hemdan; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2008</copyright-year>
<copyright-holder>Hemdan; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0"></ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
<pmc-comment>
Hemdan
YA
Nasr
nasr.hemdan@izi.fraunhofer.de
The role of interleukin-12 in the heavy metal-elicited immunomodulation: relevance of various evaluation methods
2008 Journal of Occupational Medicine and Toxicology 3(1): 25-. (2008) 1745-6673(2008)3:1<25> urn:ISSN:1745-6673 </pmc-comment>
</license>
</permissions>
<abstract><sec><title>Background</title>
<p>Increasing evidence exists that heavy metals modulate T helper cell (Th) responses and thereby elicit various pathological manifestation. Interleukin (IL)-12, a crucial innate cytokine, was found to be regulated by such xenobiotic agents. This study aimed at testing whether IL-12 profiles may be indicative of heavy metals-induced immunomodulation.</p>
</sec>
<sec sec-type="methods"><title>Methods</title>
<p>Human immunocompetent cells, activated either by monoclonal antibodies or heat-killed <italic>Salmonella enterica</italic>
, were cultured in the absence or presence of cadmium (Cd) acetate or mercuric (Hg) chloride. <italic>In vivo </italic>
experiments were set up where BALB/c mice were exposed to sub-lethal doses of Cd or Hg salts for 3 or 5 weeks. Cytotoxicity was assessed by MTT-reduction assay. Modulation of cytokine profiles was evaluated by enzyme-linked immunosorbent assay (ELISA), cytometric bead-based array (CBA) and real-time polymerase chain reaction (RT-PCR); the relevance of these methods of cytokine quantification was explored.</p>
</sec>
<sec><title>Results</title>
<p>Modulation of IL-12 profiles in Cd- or Hg-exposed human PBMC was dose-dependent and significantly related to IFN-γ levels as well as to the Th1- or Th2-polarized responses. Similarly, skewing the Th1/Th2 ratios <italic>in vivo </italic>
correlated significantly with up- or down-regulation of IL-12 levels in both cases of investigated metals.</p>
</sec>
<sec><title>Conclusion</title>
<p>It can be inferred that: (i) IL-12 profiles alone may represent a relevant indicator of heavy metal-induced immune modulation; (ii) evaluating cytokine profiles by CBA is relevant and can adequately replace other methods such as ELISA and RT-PCR in basic research as well as in immune diagnostics; and (iii) targeting IL-12 in therapeutic approaches may be promising to modify Th1/Th2-associated immune disorders.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
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